Melanoma is among the most highly "immunogenic" of human malignancies. Consistent with this concept, tumor infiltrating lymphocytes (TIL) in melanoma patients recognize tumor assisted antigens in a MHC-restricted fashion. The concept of using an adenovirus vector to express the gp75 is based on several precepts. While each of these vector systems have advantages and disadvantages, there is compelling logic for using the adenovirus (Ad) vectors. First, replication competent and deficient Ad have been used as systematic vaccines to generate T-cell immune responses against transgenes inserted into the Ad genome. Second, following transfer by an Ad vector , the Ad genome is an epi-chromosomal position, and thus expression is transient. Third, Ad vectors evoke CTL against products of this vector genome, but it is not as vigorous as the antiviral genome evoked by vaccinia vector. Last, CTL are most effectively generated when the antigen is presented in the context of class I HLA antigens, rather than class II HLA. If successful, administration of the Ad vector will result in expression of the cDNA within cells of the dermis . This should lead to immunization of against hgp, including generation of CTL directed against hgp 75, and thus "immunization" against melanoma. This has the potential to suppress the growth of existing metastases, prevent the development of new metastases, and eliminate existing tumor.